Estrogens have been demonstrated to interact with specific receptors in target cells resulting in the stimulation of gene expression. The long term goals of these studies are to further our understanding of the mechanism(s) of steroid regulation of gene expression in mammalian reproductive tissues. In response to estrogens the uterus produces and secretes a 180 kD protein which has been shown to be complement component 3 (C3). This is a cell specific estrogen induction in that synthesis occurs only in the epithelial cells of the uterus. One of the aims of these studies is to determine whether estrogens are exerting a direct effect on the uterine C3 gene or stimulating C3 gene expression through an indirect mechanism. This uterine cell specific expression will also be used to study the molecular mechanisms by which antiestrogens function as full agonists of some uterine responses but as antagonists of others. This paradox will be examined in terms of cell and gene specificity. The interaction of estradiol and progesterone regulate many of the uterine functions associated with reproduction. The underlying mechanism of this interaction will be studied using C3 as a "marker" protein. An additional specific aim of this proposal is to examine the role of this key member of the complement system in reproduction. Various components of the classical and alternative pathways have been demonstrated to be present in cells associated with reproduction such as trophoblasts and sperm. Furthermore, the concentration of many of these components are modulated either by steroids, during pregnancy, or in diseases associated with infertility such as endometriosis. Therefore, the presence and regulation of the key components of the complement pathways will be investigated with the aim of establishing the role of the complement system in reproduction. The major role of the complement system is in host defence. Whether the C3 produced by the uterine epithelial cells functions in this capacity or in some new yet to be discovered manner will be investigated.